RT Journal Article
SR Electronic
T1 Protein citrullination was introduced into animals by horizontal gene transfer from cyanobacteria
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.13.150037
DO 10.1101/2020.06.13.150037
A1 Thomas F. M. Cummings
A1 Kevin Gori
A1 Luis Sanchez-Pulido
A1 Gabriel Gavriilidis
A1 David Moi
A1 Abigail R. Wilson
A1 Elizabeth Murchison
A1 Christophe Dessimoz
A1 Chris P. Ponting
A1 Maria A. Christophorou
YR 2020
UL http://biorxiv.org/content/early/2020/06/15/2020.06.13.150037.abstract
AB Protein post-translational modifications (PTMs) add an enormous amount of sophistication to biological systems but their origins are largely unexplored. Citrullination, a key regulatory mechanism in human physiology and pathophysiology, is particularly enigmatic in an evolutionary context. The citrullinating enzymes peptidylarginine deiminases (PADIs) are ubiquitous across vertebrates but absent from yeast, worms and flies. Here, we map the surprising evolutionary trajectory of PADIs into the animal lineage. We present strong phylogenetic support for a clade encompassing animal and cyanobacterial PADIs that excludes fungal and other bacterial homologues. The animal and cyanobacterial PADIs share unique, functionally relevant synapomorphies that are absent from all other homologues. Molecular clock calculations and sequence divergence analyses using the fossil record estimate the last common ancestor of the cyanobacterial and animal PADIs to be approximately 1 billion years old, far younger than the 3.35-4.52 billion years known to separate bacterial and eukaryotic lineages. Under an assumption of vertical descent, PADI sequence change is anachronistically slow during this evolutionary time frame, even when compared to mitochondrial proteins, products of likely endosymbiont gene transfer and some of the most highly conserved proteins in life. The consilience of evidence indicates that PADIs were introduced from cyanobacteria into animals by horizontal gene transfer (HGT). The ancestral cyanobacterial protein is enzymatically active and can citrullinate eukaryotic proteins, suggesting that the PADI HGT event introduced a new catalytic capability into the regulatory repertoire of animals. This study reveals the unusual evolution of a pleiotropic protein modification with clear relevance in human physiology and disease.Competing Interest StatementThe authors have declared no competing interest.